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Biological activity of the C-1, C-3, C-25, beta-D-glucopyranosides of 1,25-dihydroxyvitamin D3

JM Londowski, SB Kost, W Meier, L Labler and R Kumar

We have shown previously that the 3-beta-D-glucopyranosides of vitamin D3, 1 alpha-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and 25- hydroxyvitamin D3 are biologically active in vivo. In order to determine whether the presence of the beta-D-glucopyranoside moiety linked to either the C-3, the C-25 or the C-1 hydroxyl function of the molecule affected the biological activity of the conjugates 1, 2, or 3 derived from 1,25-dihydroxyvitamin D3, we administered increasing amounts of compounds to vitamin D-deficient rats maintained on a low calcium diet. The aglycone, 1,25-dihydroxyvitamin D3 (4), also was administered to another group of such animals. When administered i.v., all three beta-D-glucopyranosides increased intestinal calcium transport in doses as low as 50 pmol/rat. A dose of approximately 500 pmol/rat was required to increase bone calcium mobilization in these same animals. The three glucosides were found to be equally active in both biological responses. A dose of only 5 pmol of 1,25- dihydroxyvitamin D3 (4) increased both intestinal calcium transport and bone calcium mobilization. We also performed similar experiments after the p.o. administration of these compounds to vitamin D-deficient rats maintained on a low calcium diet. The glucopyranosides 1, 2 and 3 were able to increase calcium transport in the intestine, as well as mobilize bone calcium at doses of between 500 and 5000 pmol/rat. Once again, the compounds were equipotent, but were less active than 1,25- dihydroxyvitamin D3 (4). After the i.v. or p.o. doses of the glucosides, plasma concentrations of 1,25-dihydroxyvitamin D3 increased in a dose-dependent manner. We conclude that: The C-3, C-25 and C-1 beta-D-glucopyranosides of 1,25-dihydroxyvitamin D3 are biologically active and equipotent in vivo, most likely as a result of hydrolysis to the free aglycone and they are less active than the aglycone in this respect.

Volume 237, Issue 3, pp. 837-840, 06/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


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S. Masuda, V. Byford, A. Arabian, Y. Sakai, M. B. Demay, R. St-Arnaud, and G. Jones
Altered Pharmacokinetics of 1{alpha},25-Dihydroxyvitamin D3 and 25-Hydroxyvitamin D3 in the Blood and Tissues of the 25-Hydroxyvitamin D-24-Hydroxylase (Cyp24a1) Null Mouse
Endocrinology, February 1, 2005; 146(2): 825 - 834.
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Copyright © 1986 by the American Society for Pharmacology and Experimental Therapeutics.